Stroke is responsible for more than 10% of deaths worldwide and represents one of the leading causes of disability in the developed countries. Low-degree, chronic inflammation due to the present lifestyle (diet, stress, sedentariness) have a negative impact in the vascular homeostasis and, consequently, its main outcomes (obesity, hypertension, high blood cholesterol, cigarette smoking, diabetes) have become undisputed primary risk factors for the occurrence of stroke. Indeed, atherosclerosis, the main vascular vessel pathology, results from the inflammatory build-up of lipid-laden macrophages in the vessel wall, although its precise molecular pathogenic mechanism is still poorly understood. Carotid artery atherosclerosis has become the major high risk mechanism for the occurrence of ischemic stroke, which represents more than 80% of all cerebrovascular events. Preventive measures have been developed to avoid carotid stenosis, such as surgical plaque removal by carotid endarterectomy (CEA) or endovascular stent placement (CAS), whose benefit has been suggested in several clinical trials. Nevertheless, the surgical management of asymptomatic patients with >70% carotid estenosis and <10 years of life expectancy is presently highly controversial due to the improvement of the medical treatment.
Methods for assessing the cardiovascular health of a subject comprising determination of the expression levels of particular miRNA markers (miR-378, miR-497, miR-21, miR-15b, miR-99a, miR-29a, miR-24, miR-30b, miR-29c, miR-331.3p, miR-19a, miR-22, miR-126, let-7b, miR-502.3, and miR-652) have been described in EP2510116 A2. Methods for atherosclerosis diagnosis in a subject based on expression levels of particular miRNA (miR-21, miR221) have been described in US2012196293 A1. A miRNA profiling of patients suffering from ischemic stroke has been performed by Tan et al. (Kay Sin Tan et al. 2009 Plos One 4(11): e7689). Expression of 5 miRNA (miR-125b-2*, -27a*, -422a, -488 and -627) has been shown to be consistently altered in acute stroke irrespective of age or severity or confounding metabolic complications.
The degree of carotid artery stenosis and plaque neovascularization, evaluated through imaging techniques such as contrast-enhanced ultrasound, positron emission tomography/computed tomography (PET/TC), and magnetic resonance, is being considered a most important predictor of carotid plaque vulnerability and, consequently, of increased risk of stroke in patients with carotid artery disease. However, most of the above advanced imaging techniques have not entered routine clinical practice because of its elevated costs. Additionally, a major limitation of these imaging techniques is their application only in advanced stages of atherosclerotic disease, because of its vessel wall anatomy/morphology-based predictive nature.
Thus, novel diagnostic markers using minimally invasive approaches are needed for a more specific and sensitive prediction of atherosclerosis load and progression, and particularly, to reliably identify patients with high-risk carotid plaques for early and accurate stroke risk stratification.